Genetic and environmental determinants of variation in the plasma lipidome of older Australian twins
- Centre for Healthy Brain Ageing, University of New South Wales, Australia
- The University of Adelaide, Adelaide Medical School, Discipline of Psychiatry, Australia
- Department of Psychiatry, Melbourne Medical School, The University of Melbourne, Australia
- Mathematics and Statistics, Murdoch University, Australia
- Brain and Mind Centre, The University of Sydney, Australia
- Neuroscience Research Australia, Australia
- Queensland Brain Institute, University of Queensland, Australia
- University of Melbourne Academic Unit for Psychiatry of Old Age, St George's Hospital, Australia
- University of New South Wales, Australia
Abstract
The critical role of blood lipids in a broad range of health and disease states is well recognised but less explored is the interplay of genetics and environment within the broader blood lipidome. We examined heritability of the plasma lipidome among healthy older-aged twins (75 monozygotic/55 dizygotic pairs) enrolled in the Older Australian Twins Study (OATS) and explored corresponding gene expression and DNA methylation associations. 27/209 lipids (13.3%) detected by liquid chromatography-coupled mass spectrometry (LC-MS) were significantly heritable under the classical ACE twin model (h2=0.28-0.59), which included ceramides (Cer) and triglycerides (TG). Relative to non-significantly heritable TGs, heritable TGs had a greater number of associations with gene transcripts, not directly associated with lipid metabolism, but with immune function, signalling and transcriptional regulation. Genome-wide average DNA methylation (GWAM) levels accounted for variability in some non-heritable lipids. We reveal a complex interplay of genetic and environmental influences on the ageing plasma lipidome.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
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STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets.STRING v11, https://doi.org/10.1093/nar/gky1131.
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BioGRID 3.5.187BioGRID 3.5.187, 10.1093/nar/gky1079.
Article and author information
Author details
Nicola J Armstrong
Perminder S Sachdev
Funding
National Health and Medical Research Council
- Nady Braidy
- Perminder S Sachdev
Australian Research Council
- Nady Braidy
Rebecca L. Cooper Medical Research Foundation
- Nady Braidy
- Anne Poljak
- Perminder S Sachdev
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Mone Zaidi, Icahn School of Medicine at Mount Sinai, United States
Ethics
Human subjects: OATS was approved by the Ethics Committees of the University of New South Wales and the South Eastern Sydney Local Health District (ethics approval HC17414). All work involving human participants was performed in accordance with the principles of the Declaration of Helsinki of the World Medical Association. Informed consent was obtained from all participants and/or guardians.
Version history
- Received: May 18, 2020
- Accepted: July 20, 2020
- Accepted Manuscript published: July 22, 2020 (version 1)
- Version of Record published: July 31, 2020 (version 2)
Copyright
© 2020, Wong et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Genetic and environmental determinants of variation in the plasma lipidome of older Australian twins
eLife 9:e58954.
https://doi.org/10.7554/eLife.58954
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